Prevalence and clinico-pathologic features of ALK rearrangement among adult Filipinos with non-small cell lung cancer in a Private Tertiary Care Hospital

Introduction@#With advancements in the understanding of lung cancer biology, targeted therapy has become the rule rather than the exception. Patients with ALK rearrangements are amenable to therapy with Alectinib and other ALK inhibitors, which has been associated with better patient outcomes. While ALK rearrangement should be routinely tested in non-squamous non-small cell lung cancer (NSCLC), the cost and availability of this test is a prohibitive factor, particularly in the Philippine setting.@*Objectives@#This study aimed (1) to determine the prevalence of ALK-rearranged NSCLC among adult Filipino lung cancer patients in St. Luke’s Medical Center (SLMC) from 2016 to 2018 and (2) to determine the clinico-pathologic features of adult Filipinos with ALK-rearranged NSCLC.@*Methodology@#This is a retrospective cross-sectional descriptive study wherein the prevalence of ALK-rearranged NSCLC, detected using fluorescence in-situ hybridization (FISH) or immunohistochemistry (IHC), was determined. Clinical data of patients for whom ALK testing was performed were collected. Hematoxylin and Eosin (H&E) slides were retrieved and reviewed for the presence of certain morphologic features. Patients whose H&E slides cannot be retrieved were excluded from the study. @*Results@#ALK rearrangement was seen in 7.8% (8/103) of tumors submitted for ALK testing. Patients with ALK-rearranged tumors were generally young, light smokers, and presented with advanced clinical stage. Clear cell features and solid pattern were noted in one case and three cases, respectively. However, due to small sample size, further statistical analysis could not be performed to analyze the association of these features with the presence of ALK rearrangement.@*Conclusion@#Despite a small sample size, the prevalence and clinical profile of ALK-rearranged NSCLC in our institution are congruent with those previously described in Western populations. The association of clinical profile and morphologic features with the presence of ALK rearrangement can be further explored in future studies.

Programmed Death Ligand 1 (PD-L1) expression and its association with driver mutations among patients with non-small cell lung cancer in a Private Tertiary Care Setting

Objective@#The advent of immunotherapy has significantly changed the treatment and management of patients with advanced non-small cell lung cancer (NSCLC). Prior to initiation of immunotherapy, evaluation of programmed death ligand 1 (PD-L1) expression is required. One factor that affects PD-L1 expression in NSCLC is the presence of oncogenic driver mutations; however, little data on its association is available, especially in the Philippine setting. The study aims to determine the prevalence of PD-L1 expression and its association with driver mutations among patients with non-small cell lung cancer in a private tertiary care hospital in the Philippines.@*Methodology@#The study was undertaken for a period of two years from July 2017-July 2019 at St. Luke’s Medical Center and included 446 NSCLC samples. PD-L1 was evaluated by immunohistochemistry using 22C3 anti-PD-L1 antibody clone, EnVision FLEX visualization system on Autostainer Link 48. Patient demographics and data on driver mutation testing were recorded. Statistical analysis was performed using logistic regression. @*Results@#PD-L1 expression was observed in 273 (61.20%) of 446 cases, 119 (61.20%) of which demonstrated high PD-L1 expression while 154 (34.50%) had low PD-L1 expression. There was no significant association between PD-L1 expression and EGFR mutation, ALK mutation, age, and gender. For histologic type, high PD-L1 expression was significantly associated with adenocarcinoma and non- small cell carcinoma, NOS. @*Conclusion@#The overall prevalence of PD-L1 expression in non-small cell lung carcinoma is 61.20% based on the cases included. Although we did not find an association between PD-L1 expression and EGFR and ALK mutation, our study observed that ALK-mutated NSCLCs have 4.7 odds of having high PD-L1 expression, however, a higher sample size is warranted to truly determine significant association. The outcome of this study may provide help in the stratification of patients and predict those who will benefit from immunotherapy.

Programmed Death Ligand 1 (PD-L1) expression and its association with clinicopathologic profile in patients with non-small cell lung cancer in a Philippine Tertiary Medical Center

Introduction@#The current management of advanced non-small cell lung cancer (NSCLC) includes the characterization of Programmed Death Ligand-1 (PD-L1) expression for potential immune checkpoint inhibitor treatment. There is currently no available data regarding the patterns of PD-L1 expression in NSCLC, as well as their association with clinicopathologic profile in Filipino patients.@*Methodology@#Clinicopathologic characteristics of 187 consecutive NSCLC clinical samples with PD-L1 testing using the clone 22C3 pharmaDx kit were collected. The presence of stromal tumor-infiltrating lymphocytes (TILs) were assessed in hematoxylin and eosin-stained slides. PD-L1 expression on tumor cells (TC) and stromal TILs were evaluated. @*Results@#Of the 187 cases, there were 112 males and 75 females. The mean age at diagnosis was 66.4 years old (32-92 years old). It is composed of 131 cases of Adenocarcinoma, 15 Squamous cell carcinoma, 4 Adenosquamous carcinoma, 32 Non-small cell carcinoma, not otherwise specified, 3 poorly differentiated malignancy, 1 Large cell carcinoma, and 1 Mucinous carcinoma. Specimen types included 17 pleural fluid cell blocks, 60 tumor cell block samples, and 110 tissue biopsies. Tumor cell PD-L1 expression was identified in 59.1% of the 110 tissue biopsies. PD-L1 TPS for histologic specimens are as follows: TPS >50%, TPS 1-49%, and TPS <1% were observed in 23.6%, 35.5%, and 40.9% in our lung cancer cohort, respectively. Of the 77 cytology specimens, 50.6% presented with TC PD-L1 expression. TPS for this subgroup include: 49.4% with no PD-L1 expression, 35.1% with low PD-L1 expression, and 15.6% showing high PD-L1 expression. PD-L1 expression on TC did not correlate with age, sex, or histology for both specimen type subgroups. Stromal tumor-infiltrating lymphocytes were noted in 74.5% of tissue biopsies. Tumor cell block samples did not demonstrate stromal TILs. For tissue biopsies, female gender and TPS 1-49% were more likely to have <50% PD-L1 expression on TILs.@*Conclusion@#Overall TC PD-L1 expression was observed in more than half (55.6%) of NSCLC patients in our cohort. The prognostic value of PD-L1 and clinical response to immune checkpoint inhibitors in the Filipino population needs to be further investigated.